STRUCTURE BASED DRUG DESIGNING, SCORING, AND SYNTHESIS OF SOME SUBSTITUTED SULPHONYLUREAS/GUANIDINE -BASED DERIVATIVES AS HYPOGLYCEMIC AGENTS
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2017, Vol 9, Issue 12
Abstract
Objective: The present work deals with the designing, scoring, synthesis and, characterization of 1-(4-(2-(4-Substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substitutedbenzoyl)urea (5A-5B),1-(4-(2-(4-substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substituted-benzoyl)guanidine(5C-5E) and, 1-(4-Substitutedbenzoyl)-3-(4-(2-oxo-2-(piperazin-1-yl)ethyl)phenylsulfonyl)urea (5F-5H) based derivatives as hypoglycemic agents.Methods: Docking calculations were performed to predict the binding affinity between the AKR1C1 complexes and sulphonylureas compounds using the Glide docking program. Docking studies on LigPrep treated ligands were carried out to predict the binding pocket of protein 4YVP using the docking program. The QikProp program was used to predict the ADME/T properties of the analogues. All these newly synthesized compounds were screened for their in vivo hypoglycemic activity by most relevant animal models like alloxan-induced diabetic rats by measuring blood plasma concentration compared with reference drug glibenclamide.Results: Novel compounds 1-(4-(2-(4-Substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substitutedbenzoyl)urea (5A-5B), 1-(4-(2-(4-substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substitutedbenzoyl) guanidine (5C-5E), and 1-(4-Substitutedbenzoyl)-3-(4-(2-oxo-2-(piperazin-1-yl)ethyl)phenylsulfonyl)urea (5F-5H) were synthesised and characterized using spectral and analytical data. The results of molecular docking and in vivo hypoglycemic activity, all compounds have shown considerable activity with respect to glibenclimide, but compounds 5D (52.49±7.73) and 5E(48.18±4.22)are equipotent with respect to activity as compared to standard glibenclamide(55.97±3.19).Conclusion: Compounds 5D and 5E have exhibited good hypoglycemic activity,hence both the derivatives will consider as a lead molecule and further some modification in their structures to get a more potent anti-diabetic agent.
Authors and Affiliations
Ishan Panchal, Dhrubo Jyoti Sen, Archana Navle, Umang Shah
Keywords
Related Articles
- EP ID EP575426
- DOI 10.22159/ijpps.2017v9i12.21937
- Views 54
- Downloads 0
ANTIFUNGAL SCREENING OF 61 TRADITIONAL MEDICINAL PLANTS OF 305 EXTRACTS AGAINST DERMATOPHYTIC FUNGI TRICHOPHYTON TONSURANS
Objective: Antidermatophytic activity of 305 extracts from 61 traditional medicinal plants belonging to 33 different families from Hyderabad Karnataka region was subjected to screening against Trichophyton tonsurans.Meth...
CULTURING AND SPAWNING STRATEGIES FOR CULTIVATION OF GANODERMA LUCIDUM (CURTIS) P. KARST
Objective: To access the vegetative growth of Ganoderma lucidum on ten solid media and four liquid media. Spawn development on different grains viz., wheat, barley, maize, soybean and pearl millet was also assessed for l...
SULFONES: AN IMPORTANT CLASS OF ORGANIC COMPOUNDS WITH DIVERSE BIOLOGICAL ACTIVITIES
Sulfones have been studied broadly for various biological activities primarily as anti-inflammatory, antimicrobial, anticancer, anti-HIV, antimalarial, and anti-inflammatory. The review focused on the biological activity...
INHIBITION OF TUMOUR NECROSIS FACTOR (TNF) ACTIVITY BY A NEW ERGOSTANE STEROID FROM CLEOME DROSERIFOLIA
Objective: To isolate steroidal compound from Cleome droserifolia and explore its activity against tumour necrosis factor (TNF) using molecular docking studies.Methods: Extraction of the plant material was carried using...
ORAL DIURETIC ACTIVITY OF HOT WATER EXTRACT OF H-GRADE QUILLS OF CINNAMOMUM ZEYLANICUM BLUME IN RATS
Objective: Cinnamomum zeylanicum Blume is claimed in Sri Lankan traditional medicine as a diuretic. Diuretics that are in current use possess serious adverse effects. Thus, there is a need for discovering efficacious and...